From Artery to Memory: A Comparative Review of Vascular Cognitive Impairment Surgical Models

Vascular cognitive impairment (VCI) is a broad umbrella term encompassing a spectrum of cerebrovascular diseases ranging from mild clinical cognitive impairment to advanced vascular dementia. It represents the second most prevalent etiology of dementia among older adults, following Alzheimer’s disease (AD). VCI, however, frequently coincides with AD, synergistically contributing to neurodegeneration, reductions in white matter (WM) volume, and progressive cognitive dysfunction. While the precise pathophysiology of VCI remains largely unknown, several animal models have been utilized to better understand the underlying mechanisms of the disease and develop targeted prevention and therapeutic strategies. Reproducible rodent models of common carotid artery occlusion or stenosis capture essential features of human VCI and provide a framework to examine how both transient and chronic cerebral hypoperfusion (CCH) contribute to neurodegenerative pathways and VCI-related pathologies through alterations in neural metabolism, neurotransmitter regulation, cerebral tissue damage and, ultimately, memory function. However, broad translational gaps remain between gyrencephalic humans and lissencephalic rodents, as their differing cerebrovascular architecture does not fully recapitulate the pathogenesis or clinical symptoms of VCI or vascular dementia, as a subset. As such, the objective of this review is to highlight the principal methodologies of existing VCI animal models, with particular emphasis on histological and functional consequences of CCH, while evaluating their strengths, limitations, and clinical relevance to human disease.